The project has its aim in the development of synthetic clot-dissolving agents with the final goal being the creation of a thrombus-dissolving pill. Preceding investigations with this grant have clearly shown that this ispotentially possible. It has been found that numerous asymetric organic anions, upon addition to human plasma and the plasma of certain animals, induces fibrinolytic activity and that there is a correlation between certain molecular features and this ability. This will be further explored along wth the question of whether the tendency to bindto fibrin has some bearing on the activity of the compound and whether there is a relation of the binding to fibrin and the structure o the compounds. In addition to this, the ability of thefibrinolytic compounds to diffuse or penetrate from plasma into preformed clot will be further investigated. It was discovered, by this investigator, that two structurely unrelated organic anions induce fibrinolysis in the test tube, and also in vivo by two different pathways. The potential to design molecular structures which induce fibrinolysis will be explored to the fullest extent. These studies will be combined with assessment of the platelet aggregation inhibition by the fibrinolytic compound and their effect on some clotting factors such as factor XIII. In addition, the effect of the compounds on endogenously increased fibrinolytic activity will be assessed using a newly developed rat model.